This revised competing continuation proposal is a request for funding to explore the patterns of immune, endocrine, and inflammatory changes over the postpartum period and to analyze potential relationships between these variables and trajectories as well as the development of postpartum thyroiditis (PPT), a common autoimmune disease of the postpartum. The initial funded project explored the relationship between lactation status and stress and immunity in postpartum mothers. The major findings from that cross sectional study were the presence of significant upregulation of cytokines and proteins and inflammatory responses in 4-6 week postpartum women compared to controls. This has led to the competing continuation request that seeks to explore the pattern of these changes over time, from the first week through the sixth postpartum month, in healthy control mothers and mothers at risk for PPT. This prospective approach will also allow us to examine relationships among endocrine, demographic, stress, mood and immunity variables and determine which of these variables predict and accompany onset and course of PPT. Many autoimmune diseases flare or have their onset in the postpartum, and breastfeeding increases risk. We will use PPT as a model of autoimmune disease, and identify low and high risk for PPT groups on the basis of the presence or absence of thyroid peroxidase enzyme (TPO) autoantibodies measured during pregnancy. We will prospectively study relationships between immune and inflammatory processes and trajectories, breastfeeding status, postpartum hormones, stress and dysphoric moods, general health, and the onset and course of PPT, which we anticipate will occur in about 50% of the TPO+ mothers. In addition, exploration of the normal changes in immunity, inflammation, and hormones in TPO- mothers will provide new understanding about the physiology of the postpartum, and will lay the groundwork for relating this physiology to many maternal health outcomes. The significance of this research to public health lies in the prominent incidences of autoimmune diseases in women, and the debilitating and long-term chronic illnesses that result from autoimmune processes. Genetics only plays a part in the pathogenesis of these illnesses, and the role of environment is critical to understand. The immunology and endocrinology of the postpartum provides a lens through which to study autoimmune disease, as the postpartum is a critical period for development or exacerbation of many autoimmune diseases.